Dose-Escalation Study of TPI 287 + Avastin Followed by Randomized Study of the Same Versus Avastin for Glioblastoma

Paused · Phase 1/Phase 2

Conditions studied: Glioblastoma Multiforme

In brief

This trial is divided into two parts, a dose-escalation study (phase 1) and a randomized study (phase 2). The purpose of the dose-escalation study (phase 1) is to determine the safety, maximum tolerated dose (MTD), and efficacy of TPI 287 in combination with Avastin (bevacizumab) in subjects who have glioblastoma multiforme (GBM) that has progressed following prior radiation therapy and temozolomide (TMZ). The purpose of the randomized study (phase 2) is to determine the safety and efficacy of the phase 1 MTD of TPI 287 in combination with bevacizumab versus bevacizumab alone in subjects who have GBM that has progressed following prior radiation therapy and TMZ.

Key facts

Study ID

NCT01933815

Run by

Cortice Biosciences, Inc.

People needed

92

Starts

2013-08-01

Expected to finish

2025-05-01

Last updated by the study team

2023-02-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically proven GBM
• Disease progression following radiation and TMZ
• Up to 2 prior relapses allowed
• Baseline MRI within 17 days of Day 1 \& on steroid dosage that has been stable or decreasing for at least 5 days
• Recent resection of recurrent or progressive tumor allowed as long as at least 4 weeks have elapsed from date of surgery and the subject has recovered from surgery
• Life expectancy >12 weeks
• Eighteen years old or older
• KPS equal to or greater than 70
• Recovered from toxic effects of prior therapy to < Grade 2 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) prior to Day 1. Minimum duration required between prior therapy and Day 1 is:
• At least 12 weeks from completion of radiation therapy except if there is unequivocal evidence for tumor recurrence in which case at least 4 weeks
• 4 weeks from prior cytotoxic therapy
• 4 weeks from prior experimental drug
• 6 weeks from nitrosoureas
• 3 weeks from procarbazine
• 1 week for non-cytotoxic agents, such as interferon, tamoxifen, \& cis-retinoic acid
• Adequate bone marrow function (absolute neutrophil count > 1,500/mm3 and platelet count of > 100,000/mm3), adequate liver function [ALT and AST <3 x upper limit normal (ULN), alkaline phosphatase <2 x ULN, and total bilirubin <1.5 mg/dL], \& adequate renal function (BUN and creatinine <1.5 x ULN)
• Minimum hemoglobin of 9 g/dL
• Males \& women of childbearing potential must agree to abstain from sex or use an adequate method of contraception for the duration of study, \& for 6 months after last dose of study drug
• Signed \& dated informed consent prior to Screening evaluations

You may not qualify if…

• Radiographic evidence of contrast-enhancing tumor crossing midline, leptomeningeal dissemination, gliomatosis cerebri or infratentorial tumor
• Evidence or suspicion of disease metastatic to sites remote from the supratentorial brain
• Prior treatment with bevacizumab or other anti-vascular endothelial growth factor (VEGF) drugs
• Prior treatment with tyrosine-kinase inhibitors targeting VEGF, platelet-derived growth factor, fibroblast growth factor, tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2 (TIE-2), or angiopoietin (or their receptors)
• Prior treatment with histone deacetylase inhibitors or mammalian target of rapamycin (mTOR) inhibitors
• Prior treatment with TPI 287
• Treatment with Enzyme-Inducing Anti-Epileptic Drugs within 2 weeks prior to Day 1
• Treatment with drugs or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 3A4 or cytochrome P450 2C8 within 2 weeks prior to Day 1
• Received more than one course of radiation therapy or more than a total dose of 65 Gy. May have received radiosurgery as part of initial therapy; however, the dose counts against the total dose limit.
• Prior taxane, vincristine, or other microtubule inhibitor chemotherapies for treatment of GBM or other malignancy
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
• Any condition, including the presence of clinically significant laboratory abnormalities, which places subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study, including:
• Active infection including known AIDS or Hepatitis C or with a fever ≥38.5°C within 3 days prior to enrollment
• Diseases or conditions that obscure toxicity or dangerously alter drug metabolism
• Serious intercurrent medical illness (e.g., symptomatic congestive heart failure)
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from providing informed consent
• Inadequately controlled hypertension (defined as systolic blood pressure >140 mmHg and/or diastolic blood pressure > 90 mmHg)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• History of stroke or transient ischemic attack within 6 months prior to Day1
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

Where it is running

• University of Alabama at Birmingham — Birmingham, Alabama, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• John Theurer Cancer Center at Hackensack University Medical Center — Hackensack, New Jersey, United States
• The Long Island Brain Tumor Center at Neurological Surgery, P.C. — Commack, New York, United States
• The Long Island Brain Tumor Center at Neurological Surgery, P.C. — Lake Success, New York, United States
• University of Rochester Medical Center — Rochester, New York, United States
• The Ohio State University Wexner Medical Center — Columbus, Ohio, United States
• Memorial Hermann Hospital — Houston, Texas, United States
• Swedish Neuroscience Institute — Seattle, Washington, United States

Full record on ClinicalTrials.gov

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